Neisseria meningitidis has acquired sequences within the capsule locus by horizontal genetic transfer

Background: Expression of a capsule from one of serogroups A, B, C, W, X or Y is usually required for Neisseria meningitidis ( Nme) to cause invasive meningococcal disease. The capsule is encoded by the capsule locus, cps, which is proposed to have been acquired by a formerly capsule null organism by horizontal genetic transfer (HGT) from another species. Following identification of putative capsule genes in non-pathogenic Neisseria species, this hypothesis is re-examined. Methods: Whole genome sequence data from Neisseria species, including Nme genomes from a diverse range of clonal complexes and capsule genogroups, and non- Neisseria species, were obtained from PubMLST and GenBank. Sequence alignments of genes from the meningococcal cps, and predicted orthologues in other species, were analysed using Neighbor-nets, BOOTSCANing and maximum likelihood phylogenies. Results: The meningococcal cps was highly mosaic within regions B, C and D. A subset of sequences within regions B and C were phylogenetically nested within homologous sequences belonging to N. subflava, consistent with HGT event in which N. subflava was the donor. In the cps of 23/39 isolates, the two copies of region D were highly divergent, with rfbABC’ sequences being more closely related to predicted orthologues in the proposed species N. weixii (GenBank accession number CP023429.1) than the same genes in Nme isolates lacking a capsule. There was also evidence of mosaicism in the rfbABC’ sequences of the remaining 16 isolates, as well as rfbABC from many isolates. Conclusions: Data are consistent with the en bloc acquisition of cps in meningococci from N. subflava, followed by further recombination events with other Neisseria species. Nevertheless, the data cannot refute an alternative model, in which native meningococcal capsule existed prior to undergoing HGT with N. subflava and other species. Within-genus recombination events may have given rise to the diversity of meningococcal capsule serogroups.